Université de Lyon, France.
Eur J Immunol. 2013 Jun;43(6):1667-75. doi: 10.1002/eji.201343312. Epub 2013 Apr 30.
Patrolling Ly6C(-) monocytes are blood-circulating cells that play a role in inflammation and in the defense against pathogens. Here, we show that similar to natural killer (NK) cells, patrolling monocytes express high levels of S1PR5, a G-coupled receptor for sphingosine-1 phosphate. We found that S1pr5(-/-) mice lack peripheral Ly6C(-) monocytes but have a normal number of these cells in the bone marrow (BM). Various lines of evidence exclude a direct contribution of S1PR5 in the survival of Ly6C(-) monocytes at the periphery. Rather, our data support a role for S1PR5 in the egress of Ly6C(-) monocytes from the BM. In particular, we observed a reduced frequency of patrolling monocytes in BM sinusoids of S1PR5 KO mice. Unexpectedly, S1P was not a chemoattractant for patrolling monocytes and had no significant effect on their viability in vitro. Moreover, the disruption of S1P gradients in vivo did not alter Ly6C(-) monocyte trafficking and viability. These data suggest that S1PR5 regulates the trafficking of monocytes via a mechanism independent of S1P gradients.
巡逻 Ly6C(-)单核细胞是循环血液细胞，在炎症和抵御病原体中发挥作用。在这里，我们表明类似于自然杀伤 (NK) 细胞，巡逻单核细胞表达高水平的 S1PR5，一种用于鞘氨醇-1 磷酸的 G 蛋白偶联受体。我们发现 S1pr5(-/-) 小鼠缺乏外周 Ly6C(-)单核细胞，但骨髓 (BM) 中有正常数量的这些细胞。各种证据排除了 S1PR5 在 Ly6C(-)单核细胞在外周的存活中直接发挥作用。相反，我们的数据支持 S1PR5 在 Ly6C(-)单核细胞从 BM 迁出中的作用。具体来说，我们观察到 S1PR5 KO 小鼠 BM 窦中的巡逻单核细胞频率降低。出乎意料的是，S1P 不是巡逻单核细胞的趋化因子，并且对其体外活力没有显著影响。此外，体内 S1P 梯度的破坏并没有改变 Ly6C(-)单核细胞的迁移和活力。这些数据表明，S1PR5 通过独立于 S1P 梯度的机制调节单核细胞的迁移。
